Relatively few compounds are known from the prior art which are inhibitors of the lipoxygenase enzymes. Among the lipoxygenase inhibitors known to the art are: AA-861, a 5-lipoxygenase inhibitor, disclosed in U.S. Pat. No. 4,393,075, issued July 12, 1983 to Terao et al.; pyrazolo pyridines, which are 5-lipoxygenase inhibitors, disclosed in European Patent Application of Irikura et al., Ser. No. 121,806, published Oct. 17, 1984; arachidonyl hydroxamic acid, a 5-lipoxygenase inhibitor, disclosed in E. J. Corey et al., J. Am. Chem. Soc., 106, 1503 (1984) and European Patent Application of P. H. Nelson, Ser. No. 104,468, published Apr. 4, 1984; BW755C, inhibitor of 5- and 12-lipoxygenases, disclosed in Radmark et al., FEBS Lett., 110, 213 (1980); nordihydroguariaretic acid; an inhibitor of 5- and 15-lipoxygenases, disclosed in Morris et al., Prostaglandins, 19, (1980); REV-5901, a 5-lipoxygenase inhibitor, disclosed in Coutts, Meeting Abstract 70, Prostaglandins and Leukotrienes '84, quinoline N-oxides, 5-lipoxygenase inhibitors disclosed in European patent application of Hashizumo et al., Ser. No. 128,374, published Dec. 19, 1984 and benoxaprofen, disclosed in J. Walker, Pharm. Pharmacol., 31, 778 (1979). It would be useful to have compounds which are more potent inhibitors of these enzymes.
In addition a number of compounds identified as having some lipoxygenase inhibitory activity are structurally related to arachidonic acid. Such compounds are highly susceptible to oxidation in vitro and to breakdown by conventional pathways of lipid metabolism in vivo. Thus as well as having the desired potency it would be desirable to have agents which are relatively simple in structure, and relatively resistant to oxidation and metabolism.
It is an object of the present invention to provide compounds which are highly potent inhibitors of lipoxygenase enzymes.
It is another object of this invention to provide compounds having structures which are simpler and more stable than prior art compounds having lipid-like structures.
It is yet another object of this invention to provide compounds which inhibit lipoxygenase activity in vivo.
These and other objects of this invention will be evident from the following disclosure.